| The cellular mechanisms involved in the capacity of bone to alter mass and structure in response to mechanical demands are poorly understood. The in-vivo operating cell stress derived from bone loading is likely interstitial fluid flow along the surface of osteocytes, which respond with production of signalling molecules affecting bone resorbing osteoclasts, and/or bone forming osteoblasts. Microgravity has catabolic effects on the skeleton of astronauts, which might result from a changed response of osteocytes to mechanical stimuli. In the experiment ?FLOW2? we will test whether production of early signalling molecules involved in the mechanical loading-induced osteogenic response by osteocytes is changed under microgravity compared to 1xg. Osteocytes, osteoblasts, and fibroblasts will be incubated in ?plunger-boxes? (developed by Kaiser-Italia) using plunger-activation events for single-pulse fluid-shear-stress stimulations. Preparations for FLOW2 and preliminary ground results indicate that the FLOW-setup is viable for future flight opportunity (ESA explores possible flight in October 2009). The aim of this proposal is three-fold. First, to execute FLOW2 and analyse signalling molecules from this mission. Second, to study whether possible changes in production of signalling molecules involved in the mechanical loading-induced osteogenic response by osteocytes alters bone remodeling activity of ostoblasts and/or osteoclasts. Third, to investigate, using simulated-microgravity (RPM) or hypergravity (centrifuge), whether microgravity-exposed or mechanically-activated osteocytes are capable to directly modulate osteoclast and/or osteoblast formation, and bone resorption and/or formation. Uncovering microgravity effects on the osteocyte?s response to loading and the consequence for osteoclast and osteoblast activity, significantly contributes to understanding the cellular basis for bone remodeling. |
